Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.